A Single-center, Open-label, Randomized, Controlled, Crossover Study to Explore the Nicotine Pharmacokinetic Profile and Safety of Tobacco Heating System (THS) 2.1 Compared to Conventional Cigarettes Following Single and ad Libitum Use in Smoking, But Otherwise Healthy Subjects.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Philip Morris Products S.A.
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Nicotine Cmax
Study Overview
Brief Summary
The main goal of this exploratory study is to evaluate the pharmacokinetic profile of nicotine for the candidate modified risk tobacco product THS 2.1 and for conventional cigarettes (CC).
Detailed Description
This 2-period 2-sequence cross-over clinical study intends to explore the profile of nicotine uptake (rate and extent of nicotine absorbed and associated variability) in healthy smokers switching from (CC) to THS 2.1 (single or ad libitum use) compared to smokers continuing to use CC, as a comparator. This study will serve to optimize blood sampling schedules and sample size estimation for further studies. This study will also provide preliminary information on the relationship between nicotine absorption and urge to smoke/withdrawal symptoms when using THS 2.1 as compared to CC, as well as the safety profile, which is related to the use of THS 2.1.
After screening, enrolled subjects will be admitted to the clinic for 8 days. This study duration includes 2 consecutive periods. Each period consists of 1 day for single use of the product preceded by a 24-hour nicotine deprivation, and 1 day for ad libitum product use. After leaving the clinic, the subjects will be followed up for safety over a period of 7 days.
This clinical study will be conducted in compliance with International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Good Clinical Practice), the Declaration of Helsinki as amended in 2008, and the applicable regulatory requirements.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 23 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subject has signed an informed consent form before commencement of study procedures
- •Healthy Caucasian aged between 23 to 65 years
- •Subject is current smoker for at least 3 years (based on self-reporting and biochemically verified), who, for the last 4 weeks, had smoked at least 10 commercially available non-mentholated CC per day, and is not planning to make a quit attempt within the next 3 months
Exclusion Criteria
- •As per Investigator judgment, the subject should not participate in the study for any reason (e.g. medical, psychiatric and/or social reason)
- •The subject has a medical condition requiring smoking cessation, or has a clinically relevant disease / condition which could interfere with the study participation and/or study results
- •The subject has participated in a clinical study within 3 months prior to the Screening Visit
- •Pregnant or lactating woman, and for woman of childbearing potential, absence / refusal to use an acceptable method of effective contraception
Arms & Interventions
smoking conventional cigarettes (CC)
After a 1-day nicotine deprivation, subjects are smoking one single cigarette (usual own brand) on one day and then smoking ad libitum on the subsequent day
Intervention: Conventional cigarettes (CC) (Other)
smoking conventional cigarettes (CC)
After a 1-day nicotine deprivation, subjects are smoking one single cigarette (usual own brand) on one day and then smoking ad libitum on the subsequent day
Intervention: THS 2.1 (Other)
using the Tobacco Heating System 2.1 (THS 2.1)
After a 1-day nicotine deprivation, subjects are puffing one single tobacco stick using the THS 2.1 on one day and then puffing ad libitum on the subsequent day
Intervention: Conventional cigarettes (CC) (Other)
using the Tobacco Heating System 2.1 (THS 2.1)
After a 1-day nicotine deprivation, subjects are puffing one single tobacco stick using the THS 2.1 on one day and then puffing ad libitum on the subsequent day
Intervention: THS 2.1 (Other)
Outcomes
Primary Outcomes
Nicotine Cmax
Time Frame: Single use (1 day)
Maximum plasma concentration (Cmax)
Nicotine AUC
Time Frame: Single use (1 day)
Nicotine plasma concentration, area under the curve (AUCt)
Secondary Outcomes
- Nicotine tmax(Single use (1 day))
- Safety monitoring(7 days + 7 days follow-up)
- Modified Cigarette Evaluation Questionnaire (MCEQ)(single use (1 day); multiple use (1 day))
- Nicotine concentrations(Single use (1 day); multiple use (1 day))
- Questionnaire of smoking urges (brief version) (QSU-brief)(single use (1 day); multiple use (1 day))
- Cough Visual Analog Scale(7 days)